Biochemical markers of bone turnover (BTM) are released during bone remodeling and can be measured in blood or urine as noninvasive surrogate markers for the bone remodeling rate. The C-terminal cross-linked telopeptide of type I collagen (βCTX) is released during bone resorption and is specific to bone tissue. Assays have been developed to measure βCTX in blood and in urine; most current use of βCTX measurement for research and in clinical practice is performed on a blood sample. Method-specific differences for serum and plasma βCTX have led to initiatives to standardize or harmonize βCTX commercial assays. βCTX demonstrates significant biological variation due to circadian rhythm and effect of food which can be minimized by standardized sample collection in the fasting state in the morning. While βCTX predicts fracture risk independent of bone mineral density, lack of data has precluded its inclusion in fracture risk calculators. The changes seen in βCTX with antiresorptive therapies have been well characterized and this has led to its widespread use for monitoring therapy in osteoporosis. However, more fracture-based data on appropriate treatment goals for monitoring need to be developed. Evidence is lacking for the use of βCTX in managing "drug holidays" of bisphosphonate treatment in osteoporosis or risk stratifying those at increased risk of developing osteonecrosis of the jaw. βCTX is useful as an adjunct to imaging techniques for the diagnosis of Paget's disease of bone and for monitoring therapy and detecting recurrence. βCTX also shows promise in the management of metastatic bone disease.